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Yuan, Zengqiang; Becker, Esther B.E; Merlo, Paola; Yamada, Tomoko; DiBacco, Sara; Konishi, Yoshiyuki; Schaefer, Erik M; Bonni, Azad
Science (American Association for the Advancement of Science), 03/2008, Letnik: 319, Številka: 5870Journal Article
Activation of cyclin-dependent kinase 1 (Cdk1) has been linked to cell death of postmitotic neurons in brain development and disease. We found that Cdk1 phosphorylated the transcription factor FOXO1 at Ser²⁴⁹ in vitro and in vivo. The phosphorylation of FOXO1 at Ser²⁴⁹ disrupted FOXO1 binding with 14-3-3 proteins and thereby promoted the nuclear accumulation of FOXO1 and stimulated FOXO1-dependent transcription, leading to cell death in neurons. In proliferating cells, Cdk1 induced FOXO1 Ser²⁴⁹ phosphorylation at the G₂/M phase of the cell cycle, resulting in FOXO1-dependent expression of the mitotic regulator Polo-like kinase (Plk). These findings define a conserved signaling link between Cdk1 and FOXO1 that may have a key role in diverse biological processes, including the degeneration of postmitotic neurons.
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